Allergic Rhinitis

Nasal congestion through an Allergic rhinitis model

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Compliance

Non-GLP compliant. The study is generally used in discovery-phase preclinical research.

Purpose of the Study

To induce nasal congestion in a rodent model.

Test System

  • Adult male BALB/C mice will be group-housed in normobaric, normoxic ventilated cages
  • Systemic sensitization at Days 0, 7 and 14
  • Nasal challenges during 7 days from Day 21
  • Measurements at Day 28

Study Design

  • Group 1. Healthy animals (6 mice)
  • Group 2. Nasal congestion with vehicle (8 mice)
  • Group 3. Nasal congestion with test article (8 mice)
  • Group 4. Nasal congestion with d-pseudoephedrine (positive control) – Optional group (6 mice)

Methodology

Allergic stimulus is characterized by early phase response (EPR) and late phases response (LPR). EPR occurs within minutes of exposure to the allergen and tend to produce sneezing, itching, and clear rhinorrhea; this episode lasts for 5 to 30 minutes, and then wanes. The LPR occurs 6 to 24 hours after local allergen challenge of subjects characterized by congestion, fatigue, and irritability.

In the allergic rhinitis mice model, enumerating the frequency of nasal rubbing and sneezes is a subjective but useful measure, especially for testing the EPR and therapies involving histamine- and leukotriene-dependent pathways. A change in respiratory frequency is a physiologically relevant parameter that has recently been used to estimate nasal obstruction. Decreases in respiratory frequency have been used as a surrogate marker in the EPR and LPR as mice are obligated nasal breathers.

Outcomes

  • Whole-Body plethysmograph (respiratory function; nasal resistance (PenH); sneezing)
  • Eosinophil infiltration in nasal mucosa
  • Serum level of allergen-specific IgE
  • Serum and nasal lavage Th2 cytokines (IL4, IL5 and IL13) and Th1 cytokines (IFN-y, IL12)

Statistics

All data will be expressed as the mean ± standard error of the mean (S.E.M.). Statistical analysis will be performed (ANOVA) comparing treatment groups and days post-induction.

Amount of TA Required

To be determined based on the concentrations to be tested.

Study Timeline

  • One week to finalize the protocol/formulation
  • In vivo experimental phase: 28 days (weekly preliminary updates)
  • In vitro experimental phase: 14 extra days for the cytokine quantification and NALF flow cytometry

Reporting

  • Non-audited report 4 weeks following the last measurement. This report will include all functional data as well as cytokine levels.
  • Non-audited histological report 21 days following the last measurement.